PDHB

pyruvate dehydrogenase E1 subunit beta, the group of Pyruvate dehydrogenase complex

Basic information

Region (hg38): 3:58427630-58433857

Links

ENSG00000168291 ∙ NCBI:5162 ∙ OMIM:179060 ∙ HGNC:8808 ∙ Uniprot:P11177 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• pyruvate dehydrogenase E1-beta deficiency (Strong), mode of inheritance: AR
• pyruvate dehydrogenase E1-beta deficiency (Moderate), mode of inheritance: AR
• pyruvate dehydrogenase E1-beta deficiency (Strong), mode of inheritance: AR
• pyruvate dehydrogenase E1-beta deficiency (Supportive), mode of inheritance: AR
• Leigh syndrome (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Pyruvate dehydrogensae E1-beta deficiency	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Biochemical; Neurologic	15138885; 21914562

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PDHB gene.

• Pyruvate dehydrogenase E1-beta deficiency (10 variants)
• not provided (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PDHB gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	126	2	130
missense	1	3	48	2		54
nonsense	3	5				8
start loss	1		1			2
frameshift	5	6				11
inframe indel						0
splice donor/acceptor (+/-2bp)	1	5				6
splice region			3	30		33
non coding			10	80	23	113
Total	11	19	61	208	25

Variants in PDHB

This is a list of pathogenic ClinVar variants found in the PDHB region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
3-58427667-C-CTT		Pyruvate dehydrogenase complex deficiency	Uncertain significance (Jun 14, 2016)
3-58427669-A-T		Pyruvate dehydrogenase E1-beta deficiency	Uncertain significance (Jan 13, 2018)
3-58427674-T-C		Pyruvate dehydrogenase E1-beta deficiency	Uncertain significance (Jan 12, 2018)
3-58427678-T-C		Pyruvate dehydrogenase E1-beta deficiency	Benign (Jan 12, 2018)
3-58427681-A-G		Pyruvate dehydrogenase E1-beta deficiency	Benign (Jan 13, 2018)
3-58427706-T-C		Pyruvate dehydrogenase E1-beta deficiency	Uncertain significance (Jan 13, 2018)
3-58427738-G-C		Pyruvate dehydrogenase E1-beta deficiency	Benign (Jun 14, 2018)
3-58427791-T-G		Pyruvate dehydrogenase E1-beta deficiency	Benign (Jun 23, 2018)
3-58427830-G-C			Likely benign (Dec 25, 2019)
3-58427833-A-G		Pyruvate dehydrogenase E1-beta deficiency	Likely benign (Jan 13, 2018)
3-58427835-A-C		Pyruvate dehydrogenase complex deficiency	Uncertain significance (Jun 14, 2016)
3-58427861-G-A		Pyruvate dehydrogenase E1-beta deficiency	Uncertain significance (Jan 13, 2018)
3-58427874-T-C		Pyruvate dehydrogenase E1-beta deficiency	Uncertain significance (Jan 13, 2018)
3-58427935-G-A		Pyruvate dehydrogenase E1-beta deficiency	Benign (Jan 13, 2018)
3-58427942-G-T		Pyruvate dehydrogenase E1-beta deficiency	Benign (Jan 13, 2018)
3-58427957-G-A		Pyruvate dehydrogenase E1-beta deficiency	Uncertain significance (Apr 27, 2017)
3-58428027-G-C		Pyruvate dehydrogenase complex deficiency	Uncertain significance (Sep 22, 2020)
3-58428034-C-T		Pyruvate dehydrogenase E1-beta deficiency	Likely benign (May 27, 2022)
3-58428040-A-G		Pyruvate dehydrogenase E1-beta deficiency	Likely benign (Nov 07, 2023)
3-58428045-A-G		Pyruvate dehydrogenase E1-beta deficiency	Conflicting classifications of pathogenicity (Oct 26, 2023)
3-58428046-T-A		Pyruvate dehydrogenase E1-beta deficiency	Likely benign (Sep 14, 2022)
3-58428049-T-C		Pyruvate dehydrogenase E1-beta deficiency	Likely benign (Jun 05, 2023)
3-58428057-T-C		Pyruvate dehydrogenase E1-beta deficiency	Uncertain significance (Sep 01, 2021)
3-58428061-A-G		Pyruvate dehydrogenase E1-beta deficiency	Likely benign (Apr 18, 2023)
3-58428064-T-C		Pyruvate dehydrogenase E1-beta deficiency	Uncertain significance (Apr 28, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PDHB	protein_coding	protein_coding	ENST00000302746	10	6228

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.152	0.847	125734	0	14	125748	0.0000557

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.57	139	202	0.690	0.00000975	2339
Missense in Polyphen		37	86.725	0.42664		1048
Synonymous	-0.853	74	65.2	1.13	0.00000305	703
Loss of Function	2.98	5	19.0	0.263	8.77e-7	232

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000579	0.0000579
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.0000544	0.0000544
Finnish	0.000139	0.000139
European (Non-Finnish)	0.0000616	0.0000615
Middle Eastern	0.0000544	0.0000544
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: The pyruvate dehydrogenase complex catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2), and thereby links the glycolytic pathway to the tricarboxylic cycle. {ECO:0000269|PubMed:17474719, ECO:0000269|PubMed:19081061}.
• Disease: DISEASE: Pyruvate dehydrogenase E1-beta deficiency (PDHBD) [MIM:614111]: An enzymatic defect causing primary lactic acidosis in children. It is associated with a broad clinical spectrum ranging from fatal lactic acidosis in the newborn to chronic neurologic dysfunction with structural abnormalities in the central nervous system without systemic acidosis. {ECO:0000269|PubMed:15138885}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Citrate cycle (TCA cycle) - Homo sapiens (human);Pyruvate metabolism - Homo sapiens (human);Glycolysis / Gluconeogenesis - Homo sapiens (human);Central carbon metabolism in cancer - Homo sapiens (human);HIF-1 signaling pathway - Homo sapiens (human);Glucagon signaling pathway - Homo sapiens (human);Warburg Effect;Pyruvate Dehydrogenase Complex Deficiency;Transfer of Acetyl Groups into Mitochondria;The oncogenic action of Succinate;The oncogenic action of Fumarate;Primary hyperoxaluria II, PH2;Pyruvate kinase deficiency;Pyruvate dehydrogenase deficiency (E3);Pyruvate dehydrogenase deficiency (E2);2-ketoglutarate dehydrogenase complex deficiency;Mitochondrial complex II deficiency;Fumarase deficiency;Congenital lactic acidosis;Citric Acid Cycle;Leigh Syndrome;Glutaminolysis and Cancer;The oncogenic action of 2-hydroxyglutarate;Pyruvate Metabolism;The oncogenic action of L-2-hydroxyglutarate in Hydroxygluaricaciduria;The oncogenic action of D-2-hydroxyglutarate in Hydroxygluaricaciduria ;Pyruvate Decarboxylase E1 Component Deficiency (PDHE1 Deficiency);Hereditary Leiomyomatosis and Renal Cell Carcinoma Pathway;Glycolysis and Gluconeogenesis;Signal Transduction;Regulation of pyruvate dehydrogenase (PDH) complex;Pyruvate metabolism;Pyruvate metabolism and Citric Acid (TCA) cycle;Metabolism of amino acids and derivatives;The citric acid (TCA) cycle and respiratory electron transport;Glycolysis and Gluconeogenesis;Metabolism;pyruvate decarboxylation to acetyl CoA;Glyoxylate metabolism and glycine degradation;Pyruvate metabolism;Signaling by Retinoic Acid;Signaling by Nuclear Receptors;superpathway of conversion of glucose to acetyl CoA and entry into the TCA cycle (Consensus)

Recessive Scores

• pRec: 0.447

Intolerance Scores

• loftool: 0.124
• rvis_EVS: -0.41
• rvis_percentile_EVS: 26.23

Haploinsufficiency Scores

• pHI: 0.393
• hipred: Y
• hipred_score: 0.685
• ghis: 0.658

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.990

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Pdhb

Zebrafish Information Network

• Gene name: pdhb
• Affected structure: amacrine cell
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: glucose metabolic process;acetyl-CoA biosynthetic process from pyruvate;tricarboxylic acid cycle;mitochondrial acetyl-CoA biosynthetic process from pyruvate
• Cellular component: nucleus;nucleoplasm;mitochondrion;mitochondrial matrix;pyruvate dehydrogenase complex
• Molecular function: pyruvate dehydrogenase activity;pyruvate dehydrogenase (acetyl-transferring) activity;protein binding;pyruvate dehydrogenase (NAD+) activity